US11279735B2ActiveUtilityPatentIndex 47
Cyclic peptide antibiotics
Est. expirySep 15, 2037(~11.2 yrs left)· nominal 20-yr term from priority
Inventors:HANAN EMILY JCASTANEDO GEORGETTEBRAUN MARIE-GABRIELLEGARLAND KEIRASMITH PETER ANDREWPASTOR RICHARDGIBBONS PAULCheng YunxingWU GUOSHENGFU YUHONGYUEN PO-WAI
C07D 413/12A61K 38/00C07K 11/02C07D 273/00A61P 31/00
47
PatentIndex Score
0
Cited by
9
References
28
Claims
Abstract
Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of lipoprotein signal peptidase II (LspA), a key protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1. A compound of Formula (I):
wherein:
X 1 is —O— or —NR 1a —;
X 2 is —O— or —NR 2a —;
X 3 is —O— or —NR 3a —;
X 4 is —O— or —NR 4a —;
X 5 is —O— or —NR 5a —;
X 6 is —O— or —NR 6a —;
provided that at least one of X 1 , X 2 , X 3 , X 4 , X 5 , or X 6 is —O—;
R 1a , R 2a , R 3a , R 4a , R 5a , and R 6a are each independently hydrogen or optionally substituted C 1 -C 6 alkyl;
R 1 and R 2 are each independently hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, optionally substituted (C 1 -C 6 alkyl)heteroaryl, —S(═O) 2 R a , —S(═O) 2 NR b R c , —C(═O)R a , —C(═O)OR b , —C(═O)NR b R c , or —(C═NR b )NR b R c ;
or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocycloalkyl;
R 3 and R 4 are each independently hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
or R 3 and R 4 are taken together with the carbon atom to which they are attached to form an oxo;
R 5 is hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, or optionally substituted C 2 -C 6 alkynyl;
R 6 and R 7 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
R 8 and R 9 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
R 10 and R 11 are each independently hydrogen, halogen, optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl, optionally substituted C 2 -C 20 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
R 12 and R 13 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
or R 10 and R 12 are taken together to form an optionally substituted cycloalkyl or an optionally substituted cycloalkenyl;
R 14 and R 15 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
or R 14 and R 4a are taken together with the atoms to which they are attached to form an optionally substituted heterocycloalkyl;
R 16 and R 17 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
R 18 and R 19 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
or R 18 and R 19 are taken together with the carbon atom to which they are attached to form an oxo;
each R a is independently optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
each R b and R c is independently hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
or R b and R c are taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocycloalkyl;
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.
2. The compound of claim 1 , wherein R 18 and R 19 are taken together with the carbon atom to which they are attached to form an oxo.
3. The compound of claim 1 , wherein R 18 and R 19 are hydrogen.
4. The compound of claim 1 , having the structure of Formula (Ia):
5. The compound of claim 1 , wherein R 1 , R 2 , R 5 , R 7 , R 9 , R 11 , R 13 , R 15 and R 17 are hydrogen.
6. The compound of claim 1 , having the structure of Formula (Ib):
7. The compound of claim 1 , wherein R 1a , R 2a , R 5a and R 6a are hydrogen.
8. The compound of claim 1 , having the structure of Formula (Ic):
9. The compound of claim 1 , wherein R 3 and R 4 are hydrogen and R 4a is hydrogen or C 1 -C 6 alkyl.
10. The compound of claim 1 , wherein R 6 is C 1 -C 6 alkyl optionally substituted with one, two, or three halogen, —OR b , —NR b R c , —NC(═NR b )NR b R c , —S(═O) 2 R a , —NR b S(═O) 2 R a , —S(═O) 2 NR b R c , —C(═O)R a , —OC(═O)R a , —C(═O)OR a , —OC(═O)OR b , —C(═O)NR b R c , —NR b C(═O)[(R d ) 2 ] 1-4 NR b R c , —OC[(R d ) 2 ] 2-4 OR b , —OC[(R d ) 2 ] 2-4 NR b R c , —OC[(R d ) 2 ] 2-4 OC[(R d ) 2 ] 2-4 NR b R c , —OC[(R d ) 2 ] 2-4 NC(═NR b )NR b R c , —OC(═O)NR b R c , —NR b C(═O)NR b R c , —NR b C(═O)R a , —NR b C(═O)OR b , —O-(optionally substituted heterocycloalkyl), —O-(optionally substituted aryl), —O-(optionally substituted heteroaryl), or heteroaryl; and
each R d is independently hydrogen, halogen, —OH, —OCH 3 , or C 1 -C 6 alkyl.
11. The compound of claim 1 , wherein R 6 is C 1 -C 6 alkyl optionally substituted with one, two, or three —OR b .
12. The compound of claim 1 , wherein R 6 is selected from:
13. The compound of claim 1 , wherein R 8 is hydrogen or C 1 -C 6 alkyl.
14. The compound of claim 1 , wherein R 10 is C 8 -C 12 alkyl optionally substituted with one, two, or three halogen, —OH, or —OCH 3 .
15. The compound of claim 1 , wherein R 12 is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, (C 1 -C 6 alkyl)aryl, or (C 1 -C 6 alkyl)cycloalkyl; wherein the aryl is optionally substituted with one, two, or three halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —OH, —OCH 3 , or aryl.
16. The compound of claim 1 , wherein R 14 is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or (C 1 -C 6 alkyl)cycloalkyl.
17. The compound of claim 1 , wherein R 14 is selected from:
18. The compound of claim 1 , wherein R 14 and R 4a are taken together with the atoms to which they are attached to form an optionally substituted 5- or 6-membered heterocycloalkyl.
19. The compound of claim 1 , wherein R 16 is C 1 -C 6 alkyl, (C 1 -C 6 alkyl)cycloalkyl, cycloalkyl, (C 1 -C 6 alkyl)aryl, or aryl, each optionally substituted with one, two, or three halogen, —OR b , —NR b R c , —S(═O) 2 R a , —NR b S(═O) 2 R a , —S(═O) 2 NR b R c , —C(═O)R a , —OC(═O)R a , —C(═O)OR a , —OC(═O)OR b , —C(═O)NR b R c , —OC(═O)NR b R c , —NR b C(═O)NR b R c , —NR b C(═O)R a , —NR b C(═O)OR b , or aryl.
20. The compound of claim 1 , wherein R 16 is selected from:
21. The compound of claim 1 , wherein each R a is independently C 1 -C 6 alkyl, and each R b and R c is independently hydrogen or C 1 -C 6 alkyl.
22. A compound of Formula (III):
wherein:
X 1 is —O— or —NR 1a —;
X 2 is —O— or —NR 2a —;
X 3 is —O— or —NR 3a —;
X 4 is —O— or —NR 4a —;
X 5 is —O— or —NR 5a —;
X 6 is —O— or —NR 6a —;
provided that at least one of X 1 , X 2 , X 3 , X 4 , X 5 , or X 6 is —O—;
Y is a bond or optionally substituted C 1 -C 6 alkylene;
R 2a , R 3a , R 4a , R 5a , and R 6a are each independently hydrogen or optionally substituted C 1 -C 6 alkyl;
R 1 and R 2 are each independently hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted (C 1 -C 6 alkyl)heteroaryl, —S(═O) 2 R a , —S(═O) 2 NR b R c , —C(═O)R a , —C(═O)OR b , or —C(═O)NR b R c ;
or R 1 and R 2 are taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocycloalkyl;
R 3 and R 4 are each independently hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
or R 3 and R 4 are taken together with the carbon atom to which they are attached to form an oxo;
R 5 is hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, or optionally substituted C 2 -C 6 alkynyl;
R 6 and R 7 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)aryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
R 8 and R 9 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)aryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
R 10 and R 11 are each independently hydrogen, halogen, optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl, optionally substituted C 2 -C 20 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)aryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
R 12 and R 13 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)aryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
or R 10 and R 12 are taken together to form an optionally substituted cycloalkyl or an optionally substituted cycloalkenyl;
R 14 and R 15 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)aryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
or R 14 and R 4a are taken together with the atoms to which they are attached to form an optionally substituted heterocycloalkyl;
R 17 is hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)aryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
R 18 and R 19 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
or R 18 and R 19 are taken together with the carbon atom to which they are attached to form an oxo;
R 20 is hydroxyl or —NR 1 R 2 ;
R 21 is optionally substituted cycloalkyl;
each R a is independently optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
each R b and R c is independently hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
or R b and R c are taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocycloalkyl;
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.
23. A compound of Formula (V):
wherein:
X 1 is —O— or —NR 1a —;
X 2 is —O— or —NR 2a —;
X 3 is —O— or —NR 3a —;
X 4 is —O— or —NR 4a —;
X 5 is —O— or —NR 5a —;
X 6 is —O— or —NR 6a —;
R 1a , R 2a , R 3a , R 4a , R 5a , and R 6a are each independently hydrogen or optionally substituted C 1 -C 6 alkyl;
R 3 and R 4 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
or R 3 and R 4 are taken together with the carbon atom to which they are attached to form an oxo;
R 5 is hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, or optionally substituted C 2 -C 6 alkynyl;
R 6 and R 7 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
R 8 and R 9 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
R 10 is optionally substituted C 2 -C 20 alkyl;
R 11 is hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
Z is —CR 23 R 24 , —O—, or —NR 25 —;
R 22 is optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
R 23 , R 24 , and R 25 are each independently hydrogen or optionally substituted C 1 -C 6 alkyl;
R 13 is hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
R 14 and R 15 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
or R 14 and R 4a are taken together with the atoms to which they are attached to form an optionally substituted heterocycloalkyl;
R 16 and R 17 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
R 18 and R 19 are each independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 alkyl)cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted (C 1 -C 6 alkyl)heterocycloalkyl, optionally substituted aryl, optionally substituted (C 1 -C 6 alkyl)aryl, optionally substituted heteroaryl, or optionally substituted (C 1 -C 6 alkyl)heteroaryl;
or R 18 and R 19 are taken together with the carbon atom to which they are attached to form an oxo;
each R a is independently optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
each R b and R c is independently hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
or R b and R c are taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocycloalkyl;
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.
24. A compound selected from:
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.
25. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, and a pharmaceutically acceptable excipient.
26. The compound of claim 25 , selected from:
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.
27. The compound of claim 25 , selected from:
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.
28. The compound of claim 1 , selected from:
or an enantiomer or pharmaceutically acceptable salt thereof.Cited by (0)
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